Research done in vitro has shown that GLP-1 is mildly insulinomimetic in both fat and muscle. We did a study in non- obese (ie, not insulin resistant) subjects (published J. Clin. Endocrinol. Metab, July 1998) with intravenous GLP-1 and could not demonstrate this phenomenon. However, as the subjects had normal insulin action we may not have been able to show subtle insulinomimetic actions. We therefore initiated a study in obese, non diabetic (insulin resistant, with normal blood glucose) subjects to see if GLP-1 would decrease resistance to insulin. This would also tell us if a GLP 1-like compound might not only be useful in diabetes, but also in glucose intolerance. Treatment options that are presently available for type 2 diabetes are less than perfect. The vast majority of type 2 diabetic subjects require insulin at some point in their lives because of deteriorating beta cell function. Project Number Z01AG00214-07 LCP has shown that continuous GLP-1 treatment improves glucose tolerance and increases the rate of beta cell turnover in rodents. GLP-1, given subcutaneously to humans before each meal, does lower blood sugar. But blood sugar levels rise again before the next bolus. We wished to see if GLP-1 given continuously subcutaneously would normalize and maintain a normal blood sugar. We have, therefore, initiated a study whereby GLP-1 is given continuously subcutaneously, via a Mini-Med pump (a small pump about the size of a beeper) to Type 2 diabetic subjects for 48 hours. We then investigate for insulin-secretory capacity and insulin sensitivity. These studies are on-going.